chr16-30724724-C-T

Position:

chr16-30724724-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_006662.3(SRCAP):c.5300C>T(p.Thr1767Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,614,138 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

SRCAP
NM_006662.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.132

Variant links:

Genes affected

SRCAP (HGNC:16974): (Snf2 related CREBBP activator protein) This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

SRCAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SRCAP. . Gene score misZ 2.1272 (greater than the threshold 3.09). Trascript score misZ 3.6253 (greater than threshold 3.09). GenCC has associacion of gene with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.027952433).

BP6

Variant 16-30724724-C-T is Benign according to our data. Variant chr16-30724724-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 436856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCAP	NM_006662.3 linkuse as main transcript	c.5300C>T	p.Thr1767Met	missense_variant	25/34	ENST00000262518.9	NP_006653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9 linkuse as main transcript	c.5300C>T	p.Thr1767Met	missense_variant	25/34	2	NM_006662.3	ENSP00000262518	P1	Q6ZRS2-1
SRCAP	ENST00000411466.7 linkuse as main transcript	c.5300C>T	p.Thr1767Met	missense_variant	25/34	3		ENSP00000405186	P1	Q6ZRS2-1
SRCAP	ENST00000706321.1 linkuse as main transcript	c.5300C>T	p.Thr1767Met	missense_variant	25/34			ENSP00000516346	P1	Q6ZRS2-1
SRCAP	ENST00000483083.3 linkuse as main transcript	c.4400C>T	p.Thr1467Met	missense_variant	18/18	2		ENSP00000483329

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000256

AC:

AN:

249682

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000892

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000181

AC:

264

AN:

1461786

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

141

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000118

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000911

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SRCAP-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 11, 2017

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.045

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.062

MetaRNN

Benign

0.028

T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.6

N;.

REVEL

Uncertain

0.29

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;.

Vest4

0.21

MVP

0.27

MPC

0.70

ClinPred

0.038

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over